Detection of Endoleak after Endovascular Aortic Repair through Deep Learning Based on Non-contrast CT.

OBJECTIVES: To develop and validate a deep learning model for detecting post-endovascular aortic repair (EVAR) endoleak from non-contrast CT. METHODS: This retrospective study involved 245 patients who underwent EVAR between September 2016 and December 2022. All patients underwent both non-enhanced and enhanced follow-up CT. The presence of endoleak was evaluated based on computed tomography angiography (CTA) and radiology reports. First, the aneurysm sac was segmented, and radiomic features were extracted on non-contrast CT. Statistical analysis was conducted to investigate differences in shape and density characteristics between aneurysm sacs with and without endoleak. Subsequently, a deep learning model was trained to generate predicted segmentation of the endoleak. A binary decision was made based on whether the model produced a segmentation to detect the presence of endoleak. The absence of a predicted segmentation indicated no endoleak, while the presence of a predicted segmentation indicated endoleak. Finally, the performance of the model was evaluated by comparing the predicted segmentation with the reference segmentation obtained from CTA. Model performance was assessed using metrics such as dice similarity coefficient, sensitivity, specificity, and the area under the curve (AUC). RESULTS: This study finally included 85 patients with endoleak and 82 patients without endoleak. Compared to patients without endoleak, patients with endoleak had higher CT values and greater dispersion. The AUC in validation group was 0.951, dice similarity coefficient was 0.814, sensitivity was 0.877, and specificity was 0.884. CONCLUSION: This deep learning model based on non-contrast CT can detect endoleak after EVAR with high sensitivity.

Synthesis and in vitro anticancer evaluation of novel flavonoid-based amide derivatives as regulators of the PI3K/AKT signal pathway for TNBC treatment.

Aberrant activation of the PI3K/AKT pathway is considered in many malignant tumors and plays a crucial role in mediating malignancy progression, metastasis, and chemoresistance. Consequently, development of PI3K/AKT pathway targeted drugs is currently an attractive research field for tumor treatment. In this study, twenty-six flavonoid-based amide derivatives were synthesized and evaluated for their antiproliferation effects against seven cancer cell lines, including MDA-MB-231, MCF-7, HCC1937, A549, HepG2, GTL-16 and HeLa. Among them, compound 7t possessed the best specific cytotoxicity against triple negative breast cancer MDA-MB-231 cells with an IC50 value of 1.76 ± 0.91 µM and also presented inhibitory ability on clonal-formation, migration and invasion of MDA-MB-231 cells. Further cell-based mechanistic studies demonstrated that compound 7t caused cell cycle arrest of MDA-MB-231 cells at the G0/G1 phase and induced apoptosis. Meanwhile, the western blot assay revealed that compound 7t could down-regulate the expression of p-PI3K, p-AKT, and Bcl-2 and up-regulate the production of PTEN, Bax, and caspase-3. Molecular docking also showed a possible binding mode of 7t with PI3Kα. Together, compound 7t was eligible as a potential TNBC therapeutic candidate for further development.

Modulation of lncRNA H19 enhances resveratrol-inhibited cancer cell proliferation and migration by regulating endoplasmic reticulum stress.

The phytoalexin resveratrol exhibits anti-tumour activity in many types of cancer. In this study, we showed that resveratrol suppressed the survival of gastric tumour cells both in vivo and in vitro. Resveratrol promoted apoptosis, autophagy and endoplasmic reticulum (ER) stress in a dose-dependent manner. RNA-seq analysis showed that multiple cell death signalling pathways were activated after resveratrol treatment, while the use of ER stress activators (tunicamycin and thapsigargin) in combinatorial with resveratrol led to further inhibition of cancer cell survival. Results also showed that resveratrol altered the expression of several long non-coding RNAs (lncRNAs), including MEG3, PTTG3P, GAS5, BISPR, MALAT1 and H19. Knockdown of H19 in resveratrol-treated cells further enhanced the effects of resveratrol on apoptosis, ER stress and cell cycle S-phase arrest. Furthermore, the migratory ability of resveratrol-treated cells was dramatically decreased after H19 knockdown. In conclusion, resveratrol inhibited cancer cell survival, while knockdown of lncRNA H19 resulted in increased sensitivity to resveratrol therapy.

Synthesis and biological evaluation of novel ligustrazine-chalcone derivatives as potential anti-triple negative breast cancer agents.

A series of novel ligustrazine-chalcone hybrids were synthesized and evaluated for their in vitro and in vivo antitumor activities. The results showed that most of these compounds exhibited significant in vitro cytotoxicity against MDA-MB-231, MCF-7, A549 and HepG2 cell lines with IC50 values as low as sub-micromole. Among them, compounds 6c and 6f possessed better comprehensive characteristics for the antiproliferation effects on both MDA-MB-231 (IC50: 6c, 1.60 ± 0.21 µM; 6f, 1.67 ± 1.25 µM) and MCF-7 (IC50: 6c, 1.41 ± 0.23 µM; 6f, 1.54 ± 0.30 µM). They also exhibited the potent colony-formation inhibitory abilities on above two cell lines in both concentration and time dependent manners, as well as the significantly suppression capabilities against the migration of such cell lines in a concentration dependent manner by wound-healing assay. Of note, compound 6c could significantly induce the apoptosis of MDA-MB-231 cells in a concentration dependent manner and inhibited the transformation of the growth cycle of MDA-MB-231 cells and blocked the cell growth cycle in G0/G1 phase. Moreover, the in vivo antiproliferation assay of compound 6c on TNBC model indicated such compound had a remarkable potency against tumor growth with a widely safety window. Further immunohistochemistry analysis illustrated that compound 6c was provided with a potent capacity to significantly reduce the Ki-67 positive rate in a dose dependent manner. All the results suggested that these hybrids presented both in vitro and in vivo proliferation inhibition potency against breast cancer and further development with good therapeutic potential should be of great interest.

Design, synthesis and antitumor evaluation of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives as potential c-Met inhibitors.

A series of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives (10a-10x) were designed, synthesized, and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against the SH-SY5Y, MDA-MB-231, A549, and HepG2 cell lines. Most of the compounds remarkably inhibited c-Met kinase and showed moderate to good cytotoxicity and selectivity toward the four cancer cell lines. Among them, compounds 10b and 10f were the two most potent selective c-Met inhibitors with half-maximal inhibitory concentration (IC50) values of 5.17 ± 0.48 nM and 5.62 ± 0.78 nM, respectively, and suppression abilities comparable with the positive control cabozantinib. Cell proliferation assay further demonstrated that the two most promising compounds 10a and 10b also showed good cytotoxicity and selectivity toward MDA-MB-231 cells, with IC50 values of 26.67 ± 2.56 µM and 26.83 ± 2.41 µM, respectively. Compounds 10f and 10g showed cytotoxicity and selectivity toward A549 cells, with IC50 values of 20.20 ± 2.04 µM and 21.65 ± 1.58 µM, respectively. All antiproliferative activities were within the range of those of cabozantinib. Notably, these compounds presented relatively low hepatotoxicity compared with reference drugs. Moreover, the preliminary structure-activity relationship and docking studies revealed that replacement of a nitrogen-containing heterocycle on the R2 (block A) group might improve the c-Met kinase inhibitory and antiproliferative effects in MDA-MB-231 cells, whereas displacement by a substituted benzene ring, especially for the p-fluorophenyl or 4-fluoro-3-methoxyphenyl moiety, on the R2 group enhanced cytotoxicity toward A549 cells. Together, these results suggest that 10b and 10f are promising compounds and provide a basis for their development as new antitumor agents.

Assessment of contamination source and quality control approach for polycyclic aromatic hydrocarbons in wood-pressed rapeseed oil.

Contamination sources of polycyclic aromatic hydrocarbons (PAHs) in the raw material, oil production and storage processes of wood-pressed rapeseed oil were investigated in this study. The results showed that benzo[a]pyrene (BaP) and PAH4 (sum of BaP, benzo[a]fluoranthene, benzo[b]fluoranthene and chrysene) were unevenly distributed in the kernel (0.56-0.98 and 2.84-8.64 µg/kg, respectively) and hull (1.53-3.17 and 13.49-22.31 µg/kg, respectively) of the rapeseed raw materials. The contents of BaP and PAH4 continuously increased during the process of wood-pressed rapeseed oil, ranging from 2.21 to 10.93 and 9.36 to 40.03 µg/kg, thus demonstrating that a wide range of pollution sources of PAHs existed for the test wood-pressed rapeseed oils. The initial temperature and time of roasting should be controlled at <210°C and <60 min, due to the generation of PAHs in rapeseed by over-roasting. In addition, contact tools and substance such as lubricating oil (from the mill), heat-transfer oil (from roasting machine), rubber gaskets and straws should be properly screened. The BaP and PAH4 of rapeseed placed in the roasting area increased from 0.5 to 2.24 and from 2.08 to 9.03 µg/kg, respectively. Therefore, roasting fume control and treatment systems are necessary and the roasting section should be strictly isolated from the other stages. Storage can slightly lower the PAHs amounts in the rapeseed oil, which made the contents of BaP and PAH4 decrease from 27.00 to 24.70 and from 138.63 to 117.58 µg/kg, respectively. Quality control measures of PAHs in wood-pressed rapeseed oil were proposed and implemented, and the final oil products' BaP and PAH4 were kept below 2 and 10 µg/kg, respectively, which meets the European Commission Regulation No. 835/2011.